Abstract
The RNA-binding protein (RBP) HuR is one of the most widely studied regulators of the eukaryotic posttranscriptional gene expression and it plays a physiological role in mediating the cellular response to apoptotic, proliferating and survival stimuli. Following physiological or stress stimuli, HuR protein binds to Adenylate-Urydinilate rich elements (AREs) generally contained in the 3’UTR of transcripts, then it shuttles from the nucleus to the cytoplasm and regulates the half-life and/or translation of cargo mRNAs. Derangements in sub-cellular localization and expression of HuR have been associated with the pathophysiology of many diseases and this protein has been proposed as a potential drug target. Recent findings also re-evaluated HuR as a splicing and polyadenylation factor, expanding its spectrum of functional activity up to the maturation of pre-mRNAs. In this review, we generate a comprehensive picture of HuR functionality to discuss the implications of considering HuR as pharmacological target and the detrimental or positive impact that can be expected upon its modulation. Firstly, we focus on the recent findings about the mechanistic role of HuR in the nucleus and in the regulation of long non coding RNAs; then we describe the animal models and the clinical association and significance in cancer; finally, we have reviewed the pharmacological tools that influence HuR’s post-transcriptional control and the efforts made to identify specific HuR inhibitors.
Keywords: ELAVL1, HuR, HuR activator, HuR animal models, HuR druggability, HuR inhibitor, post-transcriptional control.
Current Drug Targets
Title:Targeting the Multifaceted HuR Protein, Benefits and Caveats
Volume: 16 Issue: 5
Author(s): Chiara Zucal, Vito D’Agostino, Rosa Loffredo, Barbara Mantelli, NatthakanThongon, Preet Lal, Elisa Latorre and Alessandro Provenzani
Affiliation:
Keywords: ELAVL1, HuR, HuR activator, HuR animal models, HuR druggability, HuR inhibitor, post-transcriptional control.
Abstract: The RNA-binding protein (RBP) HuR is one of the most widely studied regulators of the eukaryotic posttranscriptional gene expression and it plays a physiological role in mediating the cellular response to apoptotic, proliferating and survival stimuli. Following physiological or stress stimuli, HuR protein binds to Adenylate-Urydinilate rich elements (AREs) generally contained in the 3’UTR of transcripts, then it shuttles from the nucleus to the cytoplasm and regulates the half-life and/or translation of cargo mRNAs. Derangements in sub-cellular localization and expression of HuR have been associated with the pathophysiology of many diseases and this protein has been proposed as a potential drug target. Recent findings also re-evaluated HuR as a splicing and polyadenylation factor, expanding its spectrum of functional activity up to the maturation of pre-mRNAs. In this review, we generate a comprehensive picture of HuR functionality to discuss the implications of considering HuR as pharmacological target and the detrimental or positive impact that can be expected upon its modulation. Firstly, we focus on the recent findings about the mechanistic role of HuR in the nucleus and in the regulation of long non coding RNAs; then we describe the animal models and the clinical association and significance in cancer; finally, we have reviewed the pharmacological tools that influence HuR’s post-transcriptional control and the efforts made to identify specific HuR inhibitors.
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Zucal Chiara, D’Agostino Vito, Loffredo Rosa, Mantelli Barbara, NatthakanThongon , Lal Preet, Latorre Elisa and Provenzani Alessandro, Targeting the Multifaceted HuR Protein, Benefits and Caveats, Current Drug Targets 2015; 16 (5) . https://dx.doi.org/10.2174/1389450116666150223163632
DOI https://dx.doi.org/10.2174/1389450116666150223163632 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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RNA Molecules in the Treatment of Human Diseases
Messenger and non-coding RNAs, including long and small transcripts, are mediators of gene expression. Gene expression at the RNA level shows significant aberrations in human diseases, including cancer, leukemia, lymphoma, cardiovascular diseases, and neurological disorders. Human transcripts serve either as biomarkers of diagnosis, prognosis, prediction of treatment response and/or therapy ...read more
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